Neuroscience_topics
Follow
Find tag "seizure"
17.6K views | +2 today
Neuroscience_topics
Neuroscience: CNS disease, pain, brain research, ion channels, synaptic transmission, channelopathies, neuronal network
Your new post is loading...
Your new post is loading...
Scooped by Julien Hering, PhD
Scoop.it!

Specific deletion of NaV1.1 sodium channels in inhibitory interneurons causes seizures and premature death in a mouse model of Dravet syndrome

Heterozygous loss-of-function mutations in the brain sodium channel NaV1.1 cause Dravet syndrome (DS), a pharmacoresistant infantile-onset epilepsy syndrome with comorbidities of cognitive impairment and premature death. Previous studies using a mouse model of DS revealed reduced sodium currents and impaired excitability in GABAergic interneurons in the hippocampus, leading to the hypothesis that impaired excitability of GABAergic inhibitory neurons is the cause of epilepsy and premature death in DS. However, other classes of GABAergic interneurons are less impaired, so the direct cause of hyperexcitability, epilepsy, and premature death has remained unresolved. We generated a floxed Scn1a mouse line and used the Cre-Lox method driven by an enhancer from the Dlx1,2 locus for conditional deletion of Scn1a in forebrain GABAergic neurons. Immunocytochemical studies demonstrated selective loss of NaV1.1 channels in GABAergic interneurons in cerebral cortex and hippocampus. Mice with this deletion died prematurely following generalized tonic-clonic seizures, and they were equally susceptible to thermal induction of seizures as mice with global deletion of Scn1a. Evidently, loss of NaV1.1 channels in forebrain GABAergic neurons is both necessary and sufficient to cause epilepsy and premature death in DS. - by Cheah CD et al.PNAS September 4, 2012 vol. 109 no. 36 14646-14651

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

GABAergic excitation after febrile seizures induces ectopic granule cells and adult epilepsy

GABAergic excitation after febrile seizures induces ectopic granule cells and adult epilepsy | Neuroscience_topics | Scoop.it

Temporal lobe epilepsy (TLE) is accompanied by an abnormal location of granule cells in the dentate gyrus. Using a rat model of complex febrile seizures, which are thought to be a precipitating insult of TLE later in life, we report that aberrant migration of neonatal-generated granule cells results in granule cell ectopia that persists into adulthood. Febrile seizures induced an upregulation of GABAA receptors (GABAA-Rs) in neonatally generated granule cells, and hyperactivation of excitatory GABAA-Rs caused a reversal in the direction of granule cell migration. This abnormal migration was prevented by RNAi-mediated knockdown of the Na+K+2Cl− co-transporter (NKCC1), which regulates the excitatory action of GABA. NKCC1 inhibition with bumetanide after febrile seizures rescued the granule cell ectopia, susceptibility to limbic seizures and development of epilepsy. Thus, this work identifies a previously unknown pathogenic role of excitatory GABAA-R signaling and highlights NKCC1 as a potential therapeutic target for preventing granule cell ectopia and the development of epilepsy after febrile seizures. - by Koyama R. et al., Nature Medicine 18, 1271–1278, 15 July 2012

more...
No comment yet.
Scooped by Julien Hering, PhD
Scoop.it!

Closed-Loop Control of Epilepsy by Transcranial Electrical Stimulation

Closed-Loop Control of Epilepsy by Transcranial Electrical Stimulation | Neuroscience_topics | Scoop.it

Many neurological and psychiatric diseases are associated with clinically detectable, altered brain dynamics. The aberrant brain activity, in principle, can be restored through electrical stimulation. In epilepsies, abnormal patterns emerge intermittently, and therefore, a closed-loop feedback brain control that leaves other aspects of brain functions unaffected is desirable. Here, we demonstrate that seizure-triggered, feedback transcranial electrical stimulation (TES) can dramatically reduce spike-and-wave episodes in a rodent model of generalized epilepsy. Closed-loop TES can be an effective clinical tool to reduce pathological brain patterns in drug-resistant patients. - by Berényi A et al., Science 10 August 2012:
Vol. 337 no. 6095 pp. 735-737

more...
No comment yet.